ENHERTU has serious Warnings and Precautions. Click here for information related to monitoring for and management of ILD/pneumonitis. Please click here for full Prescribing Information, including Boxed WARNINGS, and click here for Medication Guide.
ENHERTU has serious Warnings and Precautions. Click here for information related to monitoring for and management of ILD/pneumonitis. Please click here for full Prescribing Information, including Boxed WARNINGS, and click here for Medication Guide.
In activating HER2-mutant 2L mNSCLC at 5.4 mg/kg
The majority of adverse reactions observed were Grade ≤2
Only the results for the recommended dose of 5.4 mg/kg are described due to increased toxicity observed with the higher dose in patients with NSCLC, including ILD/pneumonitis.1
- 19% of the 101 patients treated with ENHERTU in DESTINY-Lung02 were exposed for >6 months1
- The cutoff date for safety data was March 24, 20222
Common (≥10% all Grades or ≥2% Grades 3-4) adverse reactions in DESTINY‑Lung021
Adverse reactions |
ENHERTU 5.4 mg/kg (n=101) |
||
---|---|---|---|
All Grades (%) | Grades 3 or 4 (%) | ||
Gastrointestinal disorders | Nausea | 61 | 3 |
Constipation | 31 | 1 | |
Vomitinga | 26 | 2 | |
Diarrhea | 19 | 1 | |
Stomatitisb | 12 | 0 | |
Blood and lymphatic system disorders | Anemia | 34 | 10 |
General disorders and administration site conditions | Fatiguec | 32 | 4 |
Metabolism and nutrition disorders | Decreased appetite | 30 | 1 |
Skin and subcutaneous tissue disorders | Alopecia | 21 | 0 |
Musculoskeletal and connective tissue disorders | Musculoskeletal paind | 15 | 1 |
Adverse reactions |
ENHERTU 5.4 mg/kg (n=101) |
|
---|---|---|
All Grades (%) |
Grades 3 or 4 (%) |
|
Gastrointestinal disorders | ||
Nausea | 61 | 3 |
Constipation | 31 | 1 |
Vomitinga | 26 | 2 |
Diarrhea | 19 | 1 |
Stomatitisb | 12 | 0 |
Blood and lymphatic system disorders | ||
Anemia | 34 | 10 |
General disorders and administration site conditions | ||
Fatiguec | 32 | 4 |
Metabolism and nutrition disorders | ||
Decreased appetite | 30 | 1 |
Skin and subcutaneous tissue disorders | ||
Alopecia | 21 | 0 |
Musculoskeletal and connective tissue disorders | ||
Musculoskeletal paind | 15 | 1 |
Events were graded using NCI-CTCAE v.5.0.
aIncluding vomiting and retching.
bIncluding mucosal inflammation and stomatitis.
cIncluding asthenia, fatigue, and malaise.
dIncluding back pain, musculoskeletal stiffness, musculoskeletal chest pain, arthralgia, musculoskeletal pain, myalgia, and pain in extremity.
Other clinically relevant adverse reactions reported in <10% of patients receiving ENHERTU1
- Respiratory, thoracic and mediastinal disorders: ILDe (6%), dyspnea (5%), and epistaxis (3%)
- Gastrointestinal disorders: abdominal painf (9%)
- Skin and subcutaneous disorders: rashg (3%)
- Infections and infestations: upper respiratory tract infectionh (4%)
- Nervous system disorders: headachei (4%)
eIncluding ILD that was adjudicated as ILD including pneumonitis, ILD, pulmonary toxicity, and respiratory failure.
fIncluding abdominal discomfort, abdominal pain, and upper abdominal pain.
gIncluding rash and rash maculopapular.
hIncluding upper respiratory tract infection, pharyngitis, and laryngitis.
iIncluding headache and migraine.
Serious adverse reactions occurred in 30% of patients receiving ENHERTU1
- Serious adverse reactions in >1% of patients who received ENHERTU were ILD/pneumonitis, thrombocytopenia, dyspnea, nausea, pleural effusion, and increased troponin I
- Fatality occurred in 1 patient with suspected ILD/pneumonitis (1%)
Adverse reactions requiring dose discontinuation, interruption, or reduction in DESTINY-Lung021
Selected laboratory abnormalities in patients in DESTINY-Lung021
Laboratory parameter |
ENHERTU 5.4 mg/kg (n=101)j |
||
---|---|---|---|
All Gradesk (%) | Grades 3 or 4k (%) | ||
Hematologyl | Decreased white blood cell count | 60 | 4 |
Decreased hemoglobin | 58 | 10 | |
Decreased neutrophil count | 52 | 12 | |
Decreased lymphocyte count | 43 | 16 | |
Decreased platelet count | 40 | 4 | |
Chemistry | Decreased albumin | 39 | 0 |
Increased aspartate aminotransferase | 35 | 1 | |
Increased alanine aminotransferase | 34 | 2 | |
Increased alkaline phosphatase | 22 | 0 | |
Hypokalemia | 17 | 2 |
Laboratory parameter |
ENHERTU 5.4 mg/kg (n=101)j |
|
---|---|---|
All Gradesk (%) |
Grades 3 or 4k (%) |
|
Hematologyl | ||
Decreased white blood cell count | 60 | 4 |
Decreased hemoglobin | 58 | 10 |
Decreased neutrophil count | 52 | 12 |
Decreased lymphocyte count | 43 | 16 |
Decreased platelet count | 40 | 4 |
Chemistry | ||
Decreased albumin | 39 | 0 |
Increased aspartate aminotransferase | 35 | 1 |
Increased alanine aminotransferase | 34 | 2 |
Increased alkaline phosphatase | 22 | 0 |
Hypokalemia | 17 | 2 |
jPercentages were calculated using patients with worsening laboratory values from baseline and the number of patients with both baseline and post-treatment measurements as the denominator.
kFrequencies were based on NCI-CTCAE v.5.0 grade-derived laboratory abnormalities.
lThe denominator used to calculate the rate varied from 98 to 99 based on the number of patients with a baseline value and at least 1 post-treatment value.
Drug interaction studies1
- Clinical studies: There were no clinically meaningful drug-drug interactions between ENHERTU and itraconazole (CYP3A inhibitor), or ritonavir (OATP inhibitor)
- In vitro studies: DXd did not inhibit common CYP enzymes (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A) nor did it induce CYP1A2, CYP2B6, or CYP3A
- In vitro studies: At clinically relevant concentrations, DXd has a low potential to inhibit the transporters OAT1, OAT3, OCT1, OCT2, OATP1B1, OATP1B3, MATE1, MATE2-K, P-gp, BCRP, or BSEP
- In vitro studies: DXd is a substrate of OATP1B1, OATP1B3, MATE2-K, P-gp, MRP1, and BCRP
2L, second line; HER2, human epidermal growth factor receptor 2; ILD, interstitial lung disease; mNSCLC, metastatic non-small cell lung cancer; NCI-CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events; NSCLC, non-small cell lung cancer.